A nucleic acid microarray includes a substrate and a great number of nucleic acid probes independently immobilized on the substrate. As the nucleic acid probe, cDNA or a synthetic oligonucleic acid is often used. A conventionally used microarray includes a surface-treated substrate formed of glass, silicon or the like and nucleic acid probes immobilized thereon. Recently, substrates having an improved property, for example, a gel substrate, have been used.
A method of detecting a nucleic acid by a hybridization technique is performed as follows. To nucleic acid probes immobilized to a nucleic acid microarray, nucleic acid samples, which are to be examined, are hybridized sequence-specifically. Hybrids formed by the sequence-specific hybridization are detected with a fluorescent substance or the like, and molecules having nucleotide sequences in the samples corresponding to the plurality of nucleic acid probes are examined quantitatively or qualitatively. This method is used for analyzing, for example, the expression amount of a plurality of nucleotide sequences or the sequence itself of a specific nucleotide sequence.
Conventionally, nucleic acids are detected as follows. A hybridization reaction is caused under appropriate preset conditions, and nucleic acid samples and other unnecessary substances remaining on the surface of the array are removed by washing. Thus, nucleic acid samples which form specific hybrids with the nucleic acid probes are detected. A nucleic acid probe is often designed to be complementary or identical to a nucleotide sequence desired to be detected and used for the purpose of sequence analysis, function analysis or the like. As the nucleic acid probe, a nucleic acid having a relatively long chain such as cDNA or the like, a synthetic oligonucleic acid having a relatively short chain, or the like is used. In the case where a synthetic oligonucleic acid is used as the nucleic acid probe for detecting a nucleic acid of human, mouse or other biological organism, for which the findings of gene information are accumulated, the base sequence information thereof is usable. Using such base sequence information, and in consideration of the homology or the function of the base sequence, etc., the sequence of a synthetic oligonucleic acid is designed. Thus, a nucleic acid probe can be produced.